Photoaffinity labeling identification of thyroid hormone-regulated glucocorticoid-binding peptides in rat liver endoplasmic reticulum: an oligomeric protein with high affinity for 16β-hydroxylate

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• 作者：Betancor-Hern&aacute ; ndez ; Eva ; Pí ; n ; Rubé ; n ; Henrí ; quez-Hern&aacute ; ndez ; Luis ; et. al.
• 关键词：17α ; -AA ; 17α ; -alkylated androgen derivatives ; AR ; androgen receptor ; B_max ; maximal binding ; D₂O ; deuterium oxide ; DA ; danazol ; DCC ; dextranT70-coated charcoal ; DTT ; dithiothreitol ; DEX ; dexamethasone ; 16β ; -OHST ; 16β ; -
• 刊名：The Journal of Steroid Biochemistry and Molecular Biology
• 出版年：2003
• 期刊代码：172_09600760
• 类别：med
• 出版时间：December, 2003
• 卷：87
• 期：4-5
• 页码：253-264
• 文件大小：233 K

摘要

Steroid-binding proteins unrelated to the classical nuclear receptors have been proposed to play a role in non-genomic actions of the17α-alkylated testosterone derivative (17α-AA) stanozolol (ST). We have previously reported that male rat liver endoplasmic reticulum contains two steroid-binding sites associated with high molecular mass oligomeric proteins: (1) the ST-binding protein (STBP); and (2) the low-affinity glucocorticoid-binding protein (LAGS). To further explore the role of LAGS on the mechanism of action of ST, we have now studied: (1) the interaction of ST and its hydroxylated metabolites with solubilized LAGS and the cytosolic glucocorticoid receptor (GR); and (2) the effects of hormones on the capability of STBP to bind ST. We found that, unlike 17α-methyltestosterone, neither ST nor its hydroxylated metabolites bind to GR. However, the 16β-hydroxylation of ST significantly increases the capability of LAGS to bind ST. Interestingly, 3′-hydroxylation of ST abrogates the capability of LAGS to bind ST. ST (k_i